TY - JOUR
T1 - Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk
AU - Alonso, Estella M.
AU - Whitington, Peter F.
AU - Whitington, Susan H.
AU - Rivard, Wendy A.
AU - Given, Gilbert
N1 - Funding Information:
The exact mechanism causing prolonged nonconjugated hyperbilirubinemia in otherwise healthy human milk-fed infants is yet to be determined. 13 Jaundice in affected infants is usually apparent by 1 week of life, and peak serum bilirubin concentrations occur at 2 to 3 weeks of age 3, 4; the incidence may be as high as 34%. 5 Investigation exploring the mechanism of this problem has focused mainly on iden- Supported in part by the Pediatric Liver Research Fund, University of Chicago; the Children's Research Foundation, University of Chicago; and the Johnny Genna Foundation, Chicago. Submitted for publication July 24, 1990; accepted Oct. 1, 1990. Reprint requests: Peter F. Whitington, MD, University of Chicago Medical Center, Box 107, 5825 S. Maryland, Chicago, IL 60637. 9/23/25778 tifying a substance in the milk that either inhibits hepatic glucuronosyltransferase or enhances the enterohepatic circulation of bilirubin.4 , 6-11 Unlike adults, infants have significant amounts of nonconjugated bilirubin available for reabsorption in their small intestine ~2 , 13 because of the action of mucosal/3-glucuronidase and an environment with immature bacterial flora. TM Work by Gartner et al, 11 has shown that cow milk formulas and normal human milk inhibit absorption of nonconjugated bilirubin from the small intestine of the rat, and that milk from mothers of affected infants can enhance absorption. This work estimated absorption by determining the increase in bilirubin excretion in bile above baseline when unlabeled bilirubin was administered with the test milk into the duodenum of the rat. The data obtained,
PY - 1991/3
Y1 - 1991/3
N2 - To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3±2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29±4.0% when it was administered into the duodenum with buffer, 4.67±2.4% with Similac formula, and 7.7±2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r=0.40; p=0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values >24 μmol/L (1.4 mg/dl) (r=0.55; p=0.007), whereas in those with bilirubin values ≤24 μmol/L, there was no apparent correlation. Milk was also analyzed for β-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.
AB - To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3±2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29±4.0% when it was administered into the duodenum with buffer, 4.67±2.4% with Similac formula, and 7.7±2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r=0.40; p=0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values >24 μmol/L (1.4 mg/dl) (r=0.55; p=0.007), whereas in those with bilirubin values ≤24 μmol/L, there was no apparent correlation. Milk was also analyzed for β-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.
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U2 - 10.1016/S0022-3476(05)82162-6
DO - 10.1016/S0022-3476(05)82162-6
M3 - Article
C2 - 1999786
AN - SCOPUS:0025968259
VL - 118
SP - 425
EP - 430
JO - Journal of Pediatrics
JF - Journal of Pediatrics
SN - 0022-3476
IS - 3
ER -
